This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous studies have indicated a strong relationship between sensation seeking and substance use and abuse. Sensation seeking has been defined as a personality trait that is marked by a tendency to seek out and engage in novel and varied experiences to maintain an optimal level of arousal - even if those experiences involve significant risk. Among a number of well-established personality dimensions of sensation seeking, two are especially related to susceptibility to drug use and abuse: novelty and reward seeking, and lack of control and impulsivity. Although biochemical and biological markers have long been proposed and studied extensively for sensation seeking, these models are either based on animal studies or peripheral physiological measures in humans. This application, by combining advanced functional magnetic resonance imaging (fMRI) techniques and well-established behavioral paradigms, will provide a foundation for generating hypotheses about the neurobiological markers for sensation seeking in humans. We hypothesize that as compared to low sensation seeking (LSS) individuals, high sensation seeking (HSS) individuals show greater sensitivity and stronger neural responses to positive reward, which may result in their susceptibility to initial substance use and abuse. In contrast, HSS individuals show less sensitivity to negative outcomes and reduced control to goal-irrelevant external cues in both reward and executive control tasks, which may account for their impulsivity and lack of control to resist substance abuse. We propose to achieve the following specific aims. Specific Aims: (1) To examine individual differences in neural mechanisms of reward-related decision making between the HSS and LSS groups. We predict that the delicate balance between the neural circuitries of reward seeking and sensitivity, and emotional evaluation and cognitive control of behavior - which is crucial to defend people against addictive behaviors - may be compromised in the HSS individuals. (2) To examine individual differences in neural mechanisms of attentional and executive control between the HSS and LSS groups. We predict that HSS individuals will show less efficiency of executive control network in the frontal and parietal regions, which may account for their high impulsivity and reduced ability of executive control to resist cues that induce drug use and abuse.